Plasma HDL has been inversly associated with the development of cardiovascular disease. HDL may protect against vascular disease by facilitating the transport of cholesterol from peripheral cells to the liver, a process termed reverse cholesterol transport and by protecting LDL against oxidation. HDL particles containing apolipoprotein J (apoJ) have been proposed to play a role in the prevention of oxidation of lipoproteins since paraxonase is present on apoJ particles. Two major subclasses of apoJ-containing particles are present in HDL including those that contain both apoJ and apoA-I (LpJ:A-I) and other contain apoJ but not apoA-I (LpJ). To investigate the in vivo catabolism of apoJ particles I-125- apoJ and I131-apoA-I were reassociated with plasma lipoproteins and injected into two healthy normolipidemic volunteers. Plasma samples were separated by ultracentrifugation, FPLC and immunoaffinity chromatography. I-125-apoJ in plasma was associated with LpJ:A-I and Lp-J, a lipoprotein particle slightly larger than alpha HDL analyzed by FPLC. By 2-D gel electrophoresis, the LpJ:A-I particles had alpha mobility, while the LpJ particles migrated in the prebeta region. After ultracentrifugation, 97% of labeled apoJ was located in the d>1.21g/ml in contrast to <5% of apoA-I suggesting that apoJ dissociated from the lipoprotein particles during centrifugation. During the 7 day study lipoprotein samples were fractionated by apoA-I, apoA-II and apoE immunoaffinity chromatography. The fractional catabolic rates (FCR) of plasma apoJ and apoA-I were 1.568 plus/minus 0.093/day and 0.293 plus/minus 0.029/day, respectively. The FCR of LpJ:A-I was much slower than LpJ (1.061 plus/minus 0.021/day vs 1.825 plus/minus 0.035/day, respectively). These studies have established that plasma apoJ was catabolized 5-fold faster than apoA-I. In HDL apoJ was present both on alpha migrating LpJ:A-I particles and larger prebeta LpJ particles. The catabolism of LpA-I:J was much slower than LpJ suggesting different metabolic pathways. Alterations in the distribution or metabolism of apoJ are likely to have important effects on the physiological role of apoJ in lipid metabolism and oxidation.